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Biomedical subjects

Satoru Suzuki

Publications and source records attributed to Satoru Suzuki.

52 records · Page 3Linked to original sources

Attentional selection of overlapped shapes: a study using brief shape aftereffects.

Prior studies using brief stimulus sequences revealed "opponent shape aftereffects", indicative of direct opponent coding of global shape attributes such as aspect ratio, skew, taper, curvature, and convexity (perhaps in IT). Further, aftereffects from overlapped opponent pairs of adaptor shapes (e.g., concave and convex shapes) were substantially modulated by attention [Vision Res. 41 (2001) 3883]. Hypothetically, (1) attention might weight the attended and ignored contours at early stages of processing, or (2) it might sway opposing neural activity (e.g., of convex- vs. concave-tuned units) at the stage of opponent shape coding. Attentional modulation was equivalent for opponent pairs (producing opposite aftereffects) and non-opponent pairs (producing orthogonal aftereffects) of overlapped adaptor shapes, whether convexity or aspect-ratio aftereffects were measured. Further, the degree of attentional modulation obtained for these aftereffects (approximately 60%) was comparable to that obtained for V4 cells [J. Neurosci. 19 (1999) 1736]. Taken together, differential contour weighting appears to be the primary mechanism of attentional modulation of brief shape aftereffects.

Attention↗

Bone formation following transplantation of genetically modified primary bone marrow stromal cells.

Bone marrow stromal cells contain mesenchymal stem cells that can differentiate into a variety of mesenchymal tissues; in the presence of BMP-2, for example, they differentiate into osteoblasts. We constructed replication-deficient adenoviral vectors encoding human BMP-2 (BMP-2/Ad) or BMP-4 (BMP-4/Ad) and used them to transduce primary bone marrow stromal cells from the femurs of four-week-old female C3H mice, which then expressed and processed functional BMP-2 or BMP-4 protein. Enzyme assays and histochemical staining showed both groups of cells to possess alkaline phosphatase activity, a marker of differentiation into osteoblasts, though the activity was higher in cells transduced with BMP-2/Ad. When BMP-2/Ad-transduced cells were injected into the thigh muscles of immunocompetent C3H mice, ossicle development was detected on radiographs within four weeks after injection. Moreover, histological analysis indicated that newly developed ossicles contain mature osseous components, including cortical bone and bone marrow, within eight weeks. Thus, syngeneic transplantation of genetically modified primary bone marrow stromal cells induced bone formation in immunocompetent mice, perhaps indicating its potential for use in the development of therapeutic protocols aimed at enhancing bone formation.

Adenoviridae↗

Attention during adaptation weakens negative afterimages.

The effect of attention during adaptation on subsequent negative afterimages was examined. One of 2 overlapped outline figures was attended during a 7-10-s adaptation period. When the figures were readily perceptually segregated (on the basis of color or motion), the subsequent afterimages were initially weaker for the previously attended figure. This effect was confirmed by demonstrations that the onset of a single afterimage was delayed when an afterimage inducer was attended during adaptation compared with when a central digit stream or an overlapped (brightness-balanced) figure that did not generate an afterimage was attended. The attention effect was further confirmed using a criterion-independent (dot-integration) paradigm. The fact that selective attention during adaptation weakened or delayed afterimages suggests that attention primarily facilitates the adaptation of polarity-independent processes that modulate the visibility of afterimages rather than facilitating the adaptation of polarity-selective processes that mediate the formation of afterimages.

Adaptation, Psychological↗

Hepatic lipase mutation may reduce vascular disease prevalence in hemodialysis patients with high CETP levels.

BACKGROUND: Uremic dyslipidemia characterized by reduced high-density lipoprotein (HDL) cholesterol levels is one of the major contributors to the high incidence of cardiovascular disease in hemodialysis patients. Hepatic lipase (HL), together with cholesteryl ester transfer protein (CETP), may not only promote reverse cholesterol transport but also enhance production of small, dense, more atherogenic low-density lipoprotein (LDL). A common C-514T mutation of the promoter region of the HL gene reportedly increases HDL cholesterol levels. However, whether the HL mutation is antiatherogenic or proatherogenic has remained unknown in uremic patients and the general population. METHODS: We investigated the influence of the mutation and its interaction with CETP on HDL cholesterol levels and the apparent atherosclerotic complications in 183 hemodialysis patients aged over 30 years who had received no antilipemic drugs. RESULTS: In patients with CETP levels > or =2.2 microg/mL [high CETP (HCT) group, N = 97], subjects with the TT genotype had a significantly higher level of HDL cholesterol than those without TT genotype (56.8 +/- 15.9 mg/dL vs. 45.7 +/- 13.4 mg/dL, P < 0.001), but not in patients with CETP levels <2.2 microg/mL [low CETP (LCT) group]. Multiple linear regression analysis showed that the TT genotype was a major independent positive determinant for HDL cholesterol levels in the HCT not LCT group. Among the HCT group patients, subjects with the TT genotype (N = 25) had a tendency toward lower prevalence of vascular disease than those without TT genotype (N = 72) (4.0% vs. 22.2%, P < 0.07). In this subgroup, TT genotype had an independent odds ratio of 0.041 (95% CI 0.002 to 0.75, P < 0.05) after adjusting for other risk factors. CONCLUSION: The TT genotype of HL mutation may serve as a protective factor against vascular disease by increasing HDL cholesterol levels in hemodialysis patients with higher CETP levels.

Aged↗

Tumor-specific gene therapy for undifferentiated thyroid carcinoma utilizing the telomerase reverse transcriptase promoter.

A tumor-specific targeting system for cancer gene therapy was studied using the human telomerase reverse transcriptase (hTERT) promoter. Telomerase activity is increased in most tumors but not detected in most normal cells. We developed the recombinant adenovirus, carrying human herpes simplex virus thymidine kinase gene under the control of the hTERT promoter (AdhTERTtk) to obtain restricted expression of a suicide gene only in tumor cells. We found that transcriptional activity of hTERT was 2- to 9-fold higher in undifferentiated thyroid carcinoma cell lines than that of the Simian virus 40 promoter in transient transfection assay. Undifferentiated thyroid carcinoma cell lines were infected with AdhTERTtk, and sensitivity to ganciclovir (GCV) was analyzed. Cell viability was decreased in a GCV dose-dependent manner after treatment with AdhTERTtk/GCV. The cell-killing ability of AdhTERTtk in all thyroid or nonthyroid carcinoma cell lines tested was similar to AdCMVtk, which carries herpes simplex virus thymidine kinase gene driven by the cytomegalovirus promoter. However, normal cell lines were largely unaffected by AdhTERTtk/GCV, whereas these cells were also sensitive to GCV after infection with AdCMVtk. A xenograft model was established by transplanting human differentiated or undifferentiated thyroid carcinoma cells into Balb-C nude mice. The injections of AdhTERTtk into tumors and ip administration of GCV showed significant inhibition of tumor growth, similar to AdCMVtk/GCV treatment. Systemic administrations of adenovirus and GCV to normal rats demonstrated remarkable increase of serum liver transaminase levels and severe hepatic damages in pathological examinations in AdCMVtk-injected rats but not in the AdhTERTtk group. These results indicate that the AdhTERTtk/GCV system is a promising therapy for undifferentiated thyroid carcinoma, which is one of the most malignant tumors, without damage to normal tissues.

Adenoviridae↗

Cell-specific expression of NADPH-dependent cytosolic 3,5,3'-triiodo-L-thyronine-binding protein (p38CTBP).

We have previously shown that cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) possesses a high affinity for T3 binding in the presence of nicotinamide adenine dinucleotide phosphate in vitro, and that p38CTBP increases intracellular content of T3, and suppresses T3-mediated transactivity. Screening of mRNA expression in 73 different human tIssues has demonstrated that p38CTBP mRNA is expressed at high levels in brain and heart. We have examined the intracellular localization and tissue-specific distribution of this protein by using a specific antibody against human p38CTBP. Western blotting and immunoprecipitation studies have shown that the antibody recognizes human p38CTBP. Interaction of p38CTBP with the antibody did not affect the T3-binding activity of p38CTBP, and its dimer formation in vitro. Western blotting analysis has shown that p38CTBP is expressed in brain and heart predominantly, similar to the distribution of mRNA. Immunohistochemical studies have demonstrated p38CTBP in neural cells and cardiac muscle cells. p38CTBP localizes in cytoplasm rather than in nuclei in neural cells. The evidence for the presence of tIssue-specific localization of p38CTBP has indicated that p38CTBP has a tIssue-specific function, such as the regulation of T3 delivery from cytoplasm to nuclei.

Animals↗

Sequential priming is not constrained by the shape of long-term learning curves.

When multiple stimulus-to-response (S-R) mappings are randomly intermixed and repeated in a block of trials, immediate repetitions of an aspect of a stimulus and/or a response can facilitate stimulus detection, classification, and/or response selection--known as sequential priming. In addition to these short-term effects, response times (RT) for almost any task diminish with extended practice, improvements can occur over many days, and RT learning curves typically assume exponential or power functions. We investigated whether short-term sequential priming and long-term practice modulate RT through a common mechanism, using a variant of the additive factors method. We tracked how various priming effects, presumably affecting different processing stages (e.g, stimulus selection, stimulus identification/classification, and S-R mapping), varied over training sessions as RT diminished. All the priming effects either were not reduced or reduced approximately linearly at rates much slower than those predicted by the shapes of the coresponding RT learning curves. The overall results suggest that short term sequential priming and long-term practice modulate RT through relatively separate mechanisms, even though they appear to affect a common set of behaviorally defined processing stages.

Humans↗

Evidence for perceptual "trapping" and adaptation in multistable binocular rivalry.

When a different pattern is presented to each eye, the perceived image spontaneously alternates between the two patterns (binocular rivalry); the dynamics of these bistable alternations are known to be stochastic. Examining multistable binocular rivalry (involving four dominant percepts), we demonstrated path dependence and on-line adaptation, which were equivalent whether perceived patterns were formed by single-eye dominance or by mixed-eye dominance. The spontaneous perceptual transitions tended to get trapped within a pair of related global patterns (e.g., opponent shapes and symmetric patterns), and during such trapping, the probability of returning to the repeatedly experienced patterns gradually decreased (postselection pattern adaptation). These results suggest that the structure of global shape coding and its adaptation play a critical role in directing spontaneous alternations of visual awareness in perceptual multistability.

Adaptation, Physiological↗

Overlapping features can be parsed on the basis of rapid temporal cues that produce stable emergent percepts.

When two overlapping displays alternate rapidly, it is difficult to resolve the temporal coincidence of objects, parts, or features. However, under certain conditions (at least for luminance-based stimuli) rapid temporal coincidence can be detected on the basis of stable emergent percepts in which parts that oscillate in phase appear more strongly grouped than (or appear distinct from) parts that oscillate out of phase. These emergent percepts appear as depth segregation, enhanced slow orientation rivalry, and oriented shimmer (a new phenomenon that cannot be explained in terms of conventional apparent motion or temporal contrast illusions). These percepts resulted in up to an eightfold decrease in the coincidence detection threshold (alternations as fast as 20 ms/frame or 25 Hz) relative to control conditions that did not yield them; these sensitivity enhancements are unlikely to be due to temporal probability summation. The results provide psychophysical evidence that temporal-phase information can contribute to the parsing of overlapping patterns.

Cues↗

A tandemly repeated thyroglobulin core promoter has potential to enhance efficacy for tissue-specific gene therapy for thyroid carcinomas.

Recombinant adenoviruses, carrying herpes simplex virus thymidine kinase (HSVtk) genes, were developed to evaluate the possibility of tissue-specific gene therapy for thyroid carcinomas. The HSVtk gene was driven by a minimal thyroglobulin (TG) promoter (AdTGtk) and a tandemly repeated minimal TG promoter (Ad2 x TGtk) to obtain thyroid-specific cell killing ability. The transduction of HSVtk genes by infection with Ad2 x TGtk followed by ganciclovir (GCV) treatment showed more powerful cytotoxicity for TG-producing FRTL5 cells, a rat normal thyroid cell line, and FTC-133 cells, a human follicular thyroid carcinoma cell line, than when infected with AdTGtk in vitro. The cell killing ability of Ad2 x TGtk was 10- to 30-fold higher than that of AdTGtk and similar to that of AdCMVtk, which carries HSVtk under the control of CMV promoter. Whereas after treatment with adenovirus/GCV to non-TG-producing cell lines (undifferentiated thyroid carcinoma cell lines and carcinoma cell lines from other tissues), Ad2 x TGtk and AdTGtk needed more than 100-fold concentrated GCV to reach IC(50) compared to AdCMVtk. We confirmed the enhanced efficacy of Ad2 x TGtk for tissue-specific cytotoxicity in vivo. After adenovirus/GCV treatment for FTC-133 tumor-bearing nude mice, Ad2 x TGtk enhanced tumor growth inhibition and survival rates compared to AdTGtk. Tumor growth inhibition and survival rates by Ad2 x TGtk were similar to that by AdCMVtk. Moreover, any toxic effect for rat normal tissues was not revealed after intravenous injections with Ad2 x TGtk and intraperitoneal administrations with GCV in vivo, whereas severe liver damages were observed after treatment with AdCMVtk/GCV. These data indicate a beneficial effect of Ad2 x TGtk for tissue-specific gene therapy for TG-producing thyroid carcinomas without toxicity for normal tissues.

Adenoviridae↗

New Mg2+-dependent oxytetracycline resistance determinant tet 34 in Vibrio isolates from marine fish intestinal contents.

A new oxytetracycline (OTC) resistance (Otc(r)) determinant, Tet 34, was cloned from chromosomal DNA of Vibrio sp. no. 6 isolated from intestinal contents of cultured yellowtail (Seriola quinqueradiata). The transformant, containing cloned Tet 34, could grow in broth containing 25 microg of drug per ml with 10 mM MgCl2. Tet 34 encoded an open reading frame (ORF) 154 amino acids long. The amino acid sequence of the ORF was homologous to sequences of several bacterial xanthine-guanine phosphoribosyltransferases (XPRTs), which act in purine nucleotide salvage synthesis. Mg2+ binding site residues and the active site were highly conserved in XPRT and the ORF of Tet 34. The results suggest that Tet 34 encodes a new Mg2+-dependent Otc(r) mechanism.

Amino Acid Sequence↗

Nicotinamide adenine dinucleotide phosphate-dependent cytosolic T(3) binding protein as a regulator for T(3)-mediated transactivation.

Nicotinamide adenine dinucleotide phosphate (NADPH)- dependent cytosolic T(3) binding protein (CTBP) plays a role in the regulation of nuclear transport of T(3) in vitro. However, it is not known whether CTBP regulates the T(3) action. In this study, we examined the effects of CTBP on cellular translocation of T(3) and on transcriptional activation using established CTBP-expressing CHO or GH3 cells. The expression of CTBP increased cellular and nuclear uptake of T(3) in the CTBP-expressing cells. The efflux rate was decreased by induction of CTBP. Efflux from nuclei also inhibited by induction of CTBP. Expression of CTBP suppressed the T(3)-regulated luciferase activity in GH3 cells. Suppression was observed to be related to the expression level of CTBP. T(3) induction of rat GH mRNA was lower in the cells expressing CTBP than that in CTBP-null cells. These results suggest that CTBP regulates the T(3)-induced gene expression, with which an increase in the nuclear content of the T(3) is associated. Because we observed that a part of CTBP could be transported into nuclei and that acceptor protein for CTBP is present in nuclei as previously reported, interaction of CTBP with certain proteins, including transcription factors or nuclear T(3) receptor, may contribute to the regulation.

Animals↗

Fulminant diabetes mellitus associated with pregnancy: case reports and literature review.

We report two cases of type 1 diabetes mellitus fulminantly developed as diabetic ketoacidosis (DKA) at 19 weeks of gestation and immediately after delivery. Development of type 1 diabetes around pregnancy is not rare, but its fulminant development is highly uncommon. We also review the relevant literature concerning mostly Japanese cases. In our cases, the group of patients with fulminant progressive diabetes mellitus associated with pregnancy required insulin replacement therapy even after the acute period and showed high value of pancreatic exocrine enzymes, i.e. amylase, elastase, and lipase. The phenotype of this group was similar to "nonautoimmune, fulminant type 1 diabetes" described by Imagawa et al., where the laboratory data of type 1 diabetes-related autoantibodies showed negative. It is well known that autoimmune diseases are in good control during pregnancy. Our present finding suggests that this type of fulminant type 1 diabetes mellitus associated with pregnancy might develop as a consequence of a nonautoimmune mechanism.

Adult↗

The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients.

Hyperhomocysteinemia, which results from renal impairment, may promote arteriosclerosis and glomerulosclerosis. The combined effect of renal failure and a common mutation (C677T) in the methylenetetrahydrofolate reductase gene that leads to serum homocysteine elevations in dialysis patients was investigated. Genotypes were determined at this locus in 545 dialysis patients and 676 healthy subjects, and serum concentrations of total homocysteine and folate were measured in a subgroup of 464 patients. Multiple regression analysis showed that the TT genotype and low serum folate concentration were independent positive predictors of the serum total homocysteine concentration. The negative slope of a regression line relating homocysteine and folate concentrations was significantly steeper for patients with the TT genotype than for other genotypes. Patients with the TT genotype were significantly younger at the time of the study (54.8 +/- 12.9 versus 59.6 +/- 12.3 yr; P < 0.0001) and at initiation of dialysis (46.6 +/- 16.2 versus 51.2 +/- 15.9 yr; P < 0.02) than those with other genotypes. In patients who were older at the time of the study or at initiation of dialysis, the prevalence of the TT genotype was lower than in control subjects. In the middle quartiles (37.1 to 63.0 yr) for age at the start of dialysis, the prevalence of the TT genotype was lower in patients with a longer duration of dialysis. In this cross-sectional study, genotype and serum total homocysteine concentration were not independent risk factors for vascular disease in dialysis patients. These results indicate that the methylenetetrahydrofolate reductase mutation is a significant independent predictor for serum total homocysteine concentration.

Adult↗

Concentration of marine birnavirus from seawater with a glass fiber filter precoated with bovine serum albumin.

In the present study an efficient method for sampling the marine birnavirus (MABV) gene from seawater was developed. MABV gene was monitored by a specific polymerase chain reaction. When Millipore filters were used, MABV was efficiently collected on a filter with 0.05- micro m pore size. When both millipore and glass fiber filters were used, MABV was recovered from both filters. Use of plain glass fiber filters resulted in poor recovering efficiency. However, coating the glass fiber filters with 1% bovine serum albumin trapped MABV efficiently. Combining concentration on glass fiber filters with polymerase chain reaction is quantitative, economic and fast, suggesting that this method can be used to detect genetically identified fish disease viruses, algal viruses, and phages.

Adsorption↗

Virus-like particles suppress growth of the red-tide-forming marine dinoflagellate Gymnodinium mikimotoi.

We isolated 2 virus-like agents that suppressed growth of Gymnodinium mikimotoi from coastal waters of the Uwa Sea, Japan. The agents found in the flagellate cells, named GM6 and GM7, were filterable in a 0.22-microm-pore filter with approximately 100-nm shapes. Electron microscopic observation showed the presence of virus-like particles in severely damaged G. mikimotoi cells infected by GM6. The growth-suppression activity of the agents (GM6 or GM7) was lost by heating at 50 degrees C, with treatments of DNase and protease, and filtration through a 0.05-microm filter. Our results suggest that the agents are DNA viruses infectious to and virulent for G. mikimotoi. This is the first report of a virus-like agent specific to G. mikimotoi.

Animals↗